NM_021815.5:c.-51-294A>G

Variant names:

• chr2-107987811-A-G
• rs17036563
• NM_021815.5:c.-51-294A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_021815.5(SLC5A7):​c.-51-294A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.042 in 152,294 control chromosomes in the GnomAD database, including 166 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.042 (166 hom., cov: 33)
• Consequence: SLC5A7 NM_021815.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.179
• Publications: 1 publications found

Genes affected

SLC5A7 (HGNC:14025): (solute carrier family 5 member 7) This gene encodes a sodium ion- and chloride ion-dependent high-affinity transporter that mediates choline uptake for acetylcholine synthesis in cholinergic neurons. The protein transports choline from the extracellular space into presynaptic terminals for synthesis into acetylcholine. Increased choline uptake results from increased density of this protein in synaptosomal plasma membranes in response to depolarization of cholinergic terminals. Dysfunction of cholinergic signaling has been implicated in various disorders including depression, attention-deficit disorder, and schizophrenia. An allelic variant of this gene is associated with autosomal dominant distal hereditary motor neuronopathy type VIIA. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2015]

SLC5A7 Gene-Disease associations (from GenCC):

• neuronopathy, distal hereditary motor, type 7A

  Inheritance: AD, AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen, PanelApp Australia
• congenital myasthenic syndrome 20

  Inheritance: AR Classification: STRONG Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• distal hereditary motor neuropathy type 7

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• presynaptic congenital myasthenic syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 2-107987811-A-G is Benign according to our data. Variant chr2-107987811-A-G is described in ClinVar as Benign. ClinVar VariationId is 1227315.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021815.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC5A7	NM_021815.5	MANE Select	c.-51-294A>G		intron	N/A	NP_068587.1	Q9GZV3
	SLC5A7	NM_001305005.3		c.-48-297A>G		intron	N/A	NP_001291934.1	Q9GZV3
	SLC5A7	NM_001305006.3		c.-138+1048A>G		intron	N/A	NP_001291935.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC5A7	ENST00000264047.3	TSL:1 MANE Select	c.-51-294A>G		intron	N/A	ENSP00000264047.2	Q9GZV3
	SLC5A7	ENST00000409059.5	TSL:1	c.-48-297A>G		intron	N/A	ENSP00000387346.1	Q9GZV3
	SLC5A7	ENST00000950055.1		c.-51-294A>G		intron	N/A	ENSP00000620114.1

Frequencies

GnomAD3 genomes AF: 0.0421 AC: 6400 AN: 152176 Hom.: 166 Cov.: 33

Gnomad AFR AF: 0.0362

Gnomad AMI AF: 0.0987

Gnomad AMR AF: 0.0417

Gnomad ASJ AF: 0.0461

Gnomad EAS AF: 0.0327

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.0527

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0383

Gnomad OTH AF: 0.0473

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0420 AC: 6389 AN: 152294 Hom.: 166 Cov.: 33 AF XY: 0.0443 AC XY: 3295 AN XY: 74460

African (AFR) AF: 0.0361 AC: 1500 AN: 41552

American (AMR) AF: 0.0416 AC: 636 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0461 AC: 160 AN: 3472

East Asian (EAS) AF: 0.0324 AC: 168 AN: 5182

South Asian (SAS) AF: 0.116 AC: 558 AN: 4822

European-Finnish (FIN) AF: 0.0527 AC: 559 AN: 10614

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0383 AC: 2604 AN: 68028

Other (OTH) AF: 0.0478 AC: 101 AN: 2114

Alfa AF: 0.0398 Hom.: 200

Bravo AF: 0.0373

Asia WGS AF: 0.0820 AC: 283 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	14
DANN	Benign	0.37
PhyloP100		0.18
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs17036563; hg19: chr2-108604267;